一个开源框架用于虚拟生物等价模型和临床试验设计
Abdullah Hamadeh1, Moriah Pellowe1,2, Pierre Chelle1
1School of Pharmacy, University of Waterloo, Waterloo, Ontario, Canada.
CPT: pharmacometrics & systems pharmacology
|September 24, 2025
概括
本研究介绍了VBEToolbox,这是一个用于虚拟生物等价性 (VBE) 评估的R包. 它简化了使用体外和体内数据的in silico建模,以减少药物开发的人体测试.
科学领域:
- 药理动力学和药理动力学
- 计算生物学和生物信息学
- 药物开发和监管科学 药物开发和监管科学
背景情况:
- 生物等价性 (BE) 评估传统上需要广泛的人体测试.
- 在形实验中,虚拟生物等效 (VBE) 提供了一个有希望的替代方案来减少对人类的试验.
- 为了可靠的VBE评估,需要标准化的计算工作流.
研究的目的:
- 介绍VBEToolbox R包用于标准化计算VBE工作流程.
- 整合体外和体内数据用于药理动力学模型培训和VBE.
- 展示VBE的应用,以确定必要的研究规模和统计能力.
主要方法:
- 在开放系统药理学框架内开发了VBEToolbox R包.
- 采用非参数方法来处理参数不可识别性和不确定性.
- 将体外数据 (皮肤透,溶解) 和体内数据 (吸收) 整合到机理学和生理学基础的药物动力学模型中.
- 利用临床数据推断个体间的变异性,并建立体外到体内外抽取.
主要成果:
- 通过使用体外/体内皮肤吸收模型,成功证明了丸激素皮肤配方的VBE.
- 通过将体外溶解数据整合到基于生理学的药理动力学模型,对口服布洛配方进行评估VBE.
- 展示了VBEToolbox在简化VBE工作流程和确定虚拟学习设计方面的实用性.
结论:
- VBEToolbox为计算VBE评估提供了一个标准化的框架.
- 像VBEToolbox所支持的in silico方法,可以显著减少对人类生物等价性研究的需求.
- 提出的案例研究突出了开发和应用VBE模型在药物开发中的关键考虑因素.
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